Triethylamine → HCID 73335129, compound

HRID 710618Notes

Reaction equation

HRID 710618 reaction equation
[Cl:1][C:2]1[C:3]([C:12]([F:15])([F:14])[F:13])=[N:4][N:5]([CH2:8][C:9]([OH:11])=O)[C:6]=1[CH3:7].CN(C(ON1N=[N:31][C:26]2C=[CH:28][CH:29]=[N:30][C:25]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC[N:42]([CH2:45][CH3:46])[CH2:43][CH3:44]>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:46][C:45]([N:42]2[C:43]3[CH2:44][CH2:28][CH2:29][N:30]([C:9](=[O:11])[CH2:8][N:5]4[C:6]([CH3:7])=[C:2]([Cl:1])[C:3]([C:12]([F:15])([F:14])[F:13])=[N:4]4)[C:25]=3[CH:26]=[N:31]2)=[CH:7][CH:6]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 1876853(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 73335129HCID 73335129, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

The regioisomer mixture obtained above (66 mg, approx 0.25 mmol total) was combined with 2-(4-chloro-5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetic acid (67 mg, 0.275 mmol), HATU (114 mg, 0.3 mmol), and Et3N (52 μL, 0.38 mmol) in THF (1 mL). After 90 minutes the reaction slurry was diluted with EtOAc, washed with H2O, and concentrated. The residue was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to provide two regioisomers. First eluting, Compound A: 1-[1-(4-chlorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[4-chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone was isolated as a white solid (1.7 mg). 1H NMR (400 MHz, CDCl3, mixture of rotamers) δ 8.36 (s, 0.8H), 7.59 (s, 0.2H), 7.43 (s, 4H), 5.24 (s, 0.4H), 5.13 (s, 1.6H), 3.92 (m, 0.4H), 3.85 (m, 1.6H), 2.90 (m, 1.8H), 2.77 (m, 0.2H), 2.34 (s, 2.4H), 2.32 (s, 0.6H), 2.13 (m, 1.5H), 2.05 (m, 0.5H); MS: (ES) m/z calculated for C19H17Cl2F3N5O [M+H]+ 458.1, found 458.0. Second eluting, Compound B: 1-(2-(4-chlorophenyl)-6,7-dihydro-2H-pyrazolo[4,3-b]pyridin-4(5H)-yl)-2-(4-chloro-5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)ethanone was isolated as a white solid (31.0 mg). 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 7.56 (m, 2H), 7.36 (m, 2H), 5.16 (s, 2H), 3.84 (s, 2H), 2.93 (t, J=6.6 Hz, 2H), 2.32 (s, 3H), 2.19 (m, 2H); MS: (ES) m/z calculated for C19H17Cl2F3N5O [M+H]+ 458.1, found 458.0.

Workup

  1. customThe regioisomer mixture obtained above (66 mg, approx 0.25 mmol total)
  2. washwashed with H2O
  3. concentrationconcentrated
  4. customThe residue was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)
  5. customto provide two regioisomers
  6. washFirst eluting

Sources & evidence

ORD record
ord-3170e27d40514acaadf4b85b060c7cf7
Source dataset
uspto-grants-2015_11
Patent number
US09181241B2

Reaction notes

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